Several major aspects of senile dementia are to be investigated in this project: The Alzheimer type (SDAT) accounts for about 50%, and the munti-infarct type (MID) for another 25% of the cases of this disorder, of which there are more than one million severe examples in this country. Studies of possible etiological factors in SDAT will include analysis of the transmission and nature of the agent that induces intraneuronal paired helical filaments (PHF) in tissue culture of nervous system neurons treated with aqueous extracts of Alzheimer brain. The effects of infection caused by lymphocytic choriomeningitis virus (LCMV) in cultured neurons will be studied and a search made for evidence of LCMV infection in Alzheimer's disease. Neuropeptides in cortex and deep nuclei in autopsy brain specimens from patients with SDAT, MID, and age-matched normal (AMN) controls will be measured by radioimmunoassay and mapped, using immunocytochemical techniques. Morphometric studies involving both cell and lesion counts will focus upon differences between brain showing primarily senile plaques in cortex and those showing neurofibrillary tangles and plaques, and upon involvement of deep nuclei in SDAT, and will be correlated with analysis of choline acetyltransferase (ChAT) as well as neuropsychological data. Additional neuropsychological studies will seek to identify changes characteristic of SDAT and tests that will improve diagnostic accuracy of SDAT and MID. Mechanisms of learning and memory in groups of normal and demented elderly will be investigated. A large prospective study involving 450 elderly (age 75 to 85) volunteers will seek to identify risk factors that predispose to MID. Thus this program involves studies on diagnosis, treatment, pathogenesis, and etiology of the two major forms of senile dementia.